In photoplethysmography, it is known that constant light, even that of the near infrared region, can be guided into a tissue volume and that the light emerging from the tissue can be measured or portrayed as, on the one hand, light reflected from the tissue volume. From a biophysical point of view, a constant light potential, which is modulated with respect to time and place by the biological information, for example, by the red blood dye hemoglobin, is placed in the tissue in photoplethysmography. This modulation is measured in the form of a transmission signal or a backscattered signal, the radiator and the receiver being opposite to one another or in one plane (Perinatal Medicine, 4th European Congress of Perinatal Medicine, Prague, August 1974, Georg Thieme Stuttgart Avicenum Czechoslovak Medical Press Prague, 1975, page 497; Medizintechnik 23 (1983), 76; J. Investig. Dermatol. 82 (1984) 515; Biomedizinische Technik 31 (1986), 246; Z. Klin. Med. (Berlin DDR) 43 (1988), 185, 299, 945, 1093)
A transillumination or transmission of light through the skull of a newborn with a diameter of 7.5 cm was reproduced as a "single frame image"; in addition, the transmission of the hand of an adult person was carried out at wavelengths of 840 nm and 760 nm; the penetration of the light rays was shown integrally for the status with and without hypoxia. It was also possible to differentiate a blood vessel as well as bones. The authors came to the conclusion that tissue up to several centimeters thick was sufficiently transparent for NIR radiation and permits detection of the transmitted photons, but that the spatial specificity is poor, although it is possible, in the final analysis, to resolve structures up to a depth of 1 cm (Information processing in medical imaging. Proc. of the 9th Conference, Washington, D.C., Jun. 10 to 14, 1985, Martinus Nijhoff Publish. Portrecht 1986, page 155).
The integral measurement of volumes is a common feature of these known photoplethysmographic or transillumination methods. Such an integral measurement obviously has the disadvantage that it does not measure more closely defined volumes. Measuring probes, consisting of light emitters and receivers and suitable for the measurement of microvolumes for medical investigations, are known. In these probes, the emitter and receiver are disposed immediately adjacent to one another in one plane, the light being transmitted to the measuring site by fiber-optical light guides. The measuring probe is constructed as a needle or hollow needle and, due to the provision of a diameter at the tip of 2 to 20 microns, is also suitable for detecting microstructured volume parts (German Offenlegungsschrift 3,009,901).
A disadvantage of this apparatus for the measurement of microvolume particles is the invasive or traumatic or destructive admission of the measuring probe, in the form of a hollow needle or a micropipette, to the site of the microstructure that is to be measured. If the scalp, cranium as well as the meninges must be injured with this hollow needle in order to reach the site of the measurement, for example the brain, in order thereafter to measure the brain conditionally atraumatically, then such injury is not without repercussions.
With this apparatus, light-emitting and electrically conducting substances are injected under a certain pressure into the sample that is to be investigated. For the brain, the introduction of chemical substances with this apparatus by way of injection needles or micropipettes means an intervention into the mode of functioning of this organ with the initiation of imponderable reactions. Even for the evaluation of the microcirculation of the blood, which is controlled, as is well known, in locally discrete microareas (Europ. Neurol. 20 (1981), 200), this procedure represents a possible shortcoming, which results from the measurement and possibly distorts it. Laser scanning microscopy (Chip No. 1 January (1989), which makes possible a nondestructive, repercussionless measurement of microstructures, is known. With this laser microscopy, a punctiform light source, acting over confocal system, enables surfaces, tissue, cells and microstructures within the cell even of living preparations, such as the chromosomes of an onion root, to be portrayed three dimensionally and measured at 16 different depths. The optical sections are obtained at intervals of 0.5 micrometers with a constant depth of focus. The 3-dimensional reconstruction of the individual points photographed plays a significant part. The viewing of technical materials even below the surface, for example, the alignment of enamel particles in metallic enamels, as well as the evaluation of criteria, such as the porosity, the resistance to fracture and the tear strength, are possible. If in the depth or in situ and in vivo of relative large and inhomogeneous macrostructures relatively rapid and temporal changes in microstructures of any distribution within this macrostructure are to be measured and depicted dynamically, multidimensionally, atraumatically and without repercussions in real time with relatively low radiation intensities in the milliwatt range per square centimeter per steradian, then this cannot be realized by laser microscopy. This task, namely to measure microstructures of any distribution multidimensionally in a macrostructure, can be solved partially by known magnetic resonance-tomographic methods. However, magnetic fields of several tesla, which are not without repercussions on biological structures, are required for these methods. Moreover, spectrophotometric apparatuses, which utilize light reflection or an appropriate arrangement for an noninvasive, continuous, atraumatic, in vivo application for the diagnosis of the metabolism in organs of the body, such as the brain and the heart, are known (U.S. Pat. Nos. 4,223,680, 4,281,645, 4,321,930, 4,380,240). These apparatuses apply light with two defined wavelengths to the tissue, for example in the wavelength range from of 700 to 1300 nm (in the near infrared (NIR) range). The reflection or transmission is measured with the help of light-sensitive detectors at a relatively large distance of a few centimeters from the site of entry. As a result, the spatial measurement and evaluation is integral rather than differential.
This would have the disadvantage that only the organ as a whole or large parts of the organ, that is, relatively large volumes, can be measured or portrayed. Such a large volume element cannot be used for the finely resolving tomography and multidimensional representation, especially not if the work is to be carried out with backscattered light.
It is furthermore known that, for example, for the identification of breast cancer, the breast may penetrated by NIR radiation. Here also, however, only the transmitted radiation is measured and there is no punctiform-differential measurement (DE 31 03 609). A method is also known for the evaluation of one or more tissue parts in the brain or the female breast, known algorithms being utilized for computer tomography and the radiographic principle being employed (U.S. Pat. Nos. 4,515,165, 469,275, DD 210 202, U.S. Pat. No. 4,570,638, DE 30 19 234 C2). With this method, radiation of wavelength 700-1300 nm is passed through the tissue, the radiation being attenuated on its way. The intensity of this attenuated radiation cannot be corrected.
A method and an apparatus are disclosed in German Offenlegungsschrift 3,724,593 to keep the light, differently absorbed by the sample fluid investigated, at a predetermined amount. This is done essentially by adjusting the length of the light path in the sample. Using this method or the apparatus, for which the prerequisite essentially is the change in the path length as well as the homogeneity of the sample to be investigated, the structure of the volume flow cannot be determined dynamically, if this volume flow changes spatially and phasically in an inhomogeneous structure in the millisecond range.
There are also doubts as to whether it would be technically feasible to change the wavelength of light in an inhomogeneous body without having to change the volume that must be measured. However, inhomogeneous, different volumes do not exhibit any proportionality of the light attenuation which can be realted to the volume. For determining the blood-flow rate in large and small vessels, the Doppler flow method is known (Bibliotheca. anat. No. 18, Krager, Basel 1979, page 16; Therapiewoche 32 (1982), 5082; Int. J. Microzirkulation: Clin. exp. 5 (1986), 73; Investig. Dermatol. 82 (1984), 515). With this method, it is possible to measure the velocity of the blood corpuscle flow in the microvessels. It is a disadvantage of this method that the slow flow velocities cannot be separated and must also be measured. Here also, the Doppler flow method measures only the flow velocity of the blood components in the vessels; the actual volume flow of the red blood cells, that is, the amount of red blood cells, which infiltrates a certain cross section in a certain time, is slight relative to the flow velocity for a narrow microvessel but large relative to the flow velocity for a wide microvessel and cannot be determined with the Doppler flow method. This means that the flow velocities of the red blood cells in the vascular system are to be delineated from the volume flow through the vascular system. This volume flow affects cellular as well as noncellular constituents of the blood. In the macrovascular system, the volume flow can be measured with flow meters, if the Hagen-Poiseuille Law is taken into account. In the microcirculation region, the individual parameters no longer obey the law cited, but show deviations (Dtsch. Arch. f. Klin. Medizin 169 (1930), 212; Klin. Wschr. 7 (1928) 100). In addition, methods are known for determining the blood flow, which give information about the total flow magnitude of the volume flow, that is, of cellular and noncellular components of the blood. No distinction is made between measuring the volume flow of the red blood cells and the volume flow of the noncellular blood plasma. The blood flow is given in mL per 100 g of tissue per minute and determined nonselectively in the overall vascular system, for example, with the .sup.133 xenon isotope method (J. Neurol. Neurosurg. Psychiat. 35 (1972), 285; L'Encephale 4 (1978), 233; Brain 94 (1971), 635).
For a newer, computer-tomographic method of measuring the blood flow through the brain, namely "xenon computer tomography", nonradioactive xenon is inhaled and the blood is saturated with xenon, which in this way reaches all organs, including also the brain. The rate, at which xenon accumulates in the tissue, is a measure of the blood circulation (Chip No. 8--August 1988, pages 241-244). The additional inhalation of a nonradioactive gas is obviously a disadvantage here.